About 800,000 people in the United States population suffer from insulin deficiency diabetes (also known as juvenile or type I diabetes), and about 30,000 new cases arise each year. Further, an extremely large and rapidly increasing number of patients have forms of type II diabetes (also called adult onset or insulin-resistance diabetes), in this population at a level of epidemic proportions, that cause pancreatic exhaustion and insulin insufficiency. Diabetes type I is generally treated with insulin injection in response to blood glucose levels determined by patient glucose self-monitoring. A variety of forms of insulin, for example, slow and fast acting, and systems and devices suitable for insulin delivery by injection, for example a delivery pen, are used by the growing population of diabetics.
The abnormally high blood glucose (hyperglycemia) that characterizes diabetes, if left untreated, results in a variety of pathological conditions, for example, non-healing peripheral vascular ulcers, retinal damage leading to blindness, and kidney failure. Multiple daily doses of insulin administration by the patient, in response to frequent glucose self-monitoring per day, are required on a lifetime basis, with concomitant expense and inconvenience to the patient and the health care system. Further, greater pathological consequences of diabetes are correlated with less rigorous control of blood glucose level, control being accomplished by glucose level monitoring and insulin administration, and by dietary restrictions, so that only the compliant patients avoid negative outcomes.
Alternative diabetes therapies to glucose monitoring and insulin injection have been sought, for example, in which the diabetes patient receives a transplant of pancreatic material. These possibilities offer the potential advantage of a normal physiological response, viz., rapid release of insulin in response to increased blood glucose concentration. Transplants of allogenic or xenograft pancreatic material, such as encapsulated porcine islets or islet duct cells that have been induced to differentiate in vitro, remain experimental. Transplantation of human pancreatic material remains limited by severe insufficiency of available material and immune rejection. Transplantation of allogenic or xenograft pancreatic islet tissue remains limited because of immune rejection of the transplant, or possible transmission of an animal virus.
Transgenic mice expressing both TGFα and gastrin recombinant genes have increased pancreatic islet mass, which does not occur in mice expressing either agent alone (U.S. Pat. Nos. 5,885,956, issued Mar. 23, 1999 and 6,288,301, issued Sep. 11, 2001). Therapeutic compositions and methods for controlling blood glucose and remediating insulin insufficiency, particularly compositions and methods that can cause rapid release of insulin in response to elevated blood glucose, and that are effective for an extended period of time, remain important medical priorities.